Brain Tryptophan Metabolism on the 5‐hydroxytryptamine and Kynurenine Pathways in a Strain of Rats With a Deficiency in Platelet 5‐ht

Abstract

Brain 5‐hydroxytryptamine (5‐HT) metabolism has been compared in albino (Sprague‐Dawley; SD) and in Fawn‐Hooded (FH) rats, which have an inherited platelet 5‐HT deficiency. It was confirmed that blood 5‐HT levels in the FH rats were about one quarter of those in the SD rats. Brain 5‐HT and 5‐HIAA were however higher in FH rats on a per gram basis; there was no difference between the strains on a per brain basis, because of the smaller brain weights of the FH rats. Brain and plasma tryptophan were not significantly different in the two strains. Plasma kynur‐enine was higher in the FH rats, and brain kynurenine was also higher either on a per gram or on a per brain basis. The reserpine‐releasable brain 5‐HT was the same proportion of total brain 5‐HT in the two strains. Experiments with pargyline suggested that the turnover of 5‐HT was somewhat higher in the FH rats on a per gram basis, but not significantly so on a per brain basis. It is concluded that although brain tryptophan metabolism may be somewhat accelerated along both the 5‐HT and kynurenine pathways in the FH rats there is no gross deficiency in the binding of 5‐HT in their brains analogous to that found in their platelets.

A new inbred strain of Fawn-Hooded rats demonstrates mania-like behavioural and monoaminergic abnormalities

“…In contrast to body weight, the FH/HamSlc rats exhibited a lower brain weight than the F344 rats (Table 1). This is concordant with a previous study that reported a reduced brain volume in FH rats compared to Sprague-Dawley rats (Joseph, 1978). Neural loss or brain atrophy is also often observed in patients with depression and bipolar disorder (Bora et al, 2010; Selvaraj et al, 2012).…”

“…FH rats have a spontaneous mutation of the recessive red-eyed dilution gene (also known as Rab38 ) on chromosome 1 (Prieur and Meyers, 1984) and exhibit dysfunctional 5-HT release from platelets, as well as serotoninergic system alterations in the central nervous system (Gudelsky et al, 1985; Joseph, 1978; Tschopp and Zucker, 1972). Consistent with previous studies (Joseph, 1978), we found a reduction in plasma 5-HT levels in the FH/HamSlc rats compared with the F344 rats (Table 2). Furthermore, the concentration of tryptophan was low in the plasma but high in the brain, particularly in the prefrontal cortex (Table 2, Table 3).…”

“…One reason for this may be that the monoaminergic systems might undergo functional compensation through alterations in the number and/or sensitisation of receptors and transporters. FH rats show alterations in responses to serotoninergic agents, indicating altered 5-HT receptor sensitivity in the central nervous system (Gudelsky et al, 1985; Joseph, 1978). As for the absence of cognitive abnormalities, another reason may be that this test takes advantage of the rats’ innate behaviour and therefore represents a task with low cognitive load.…”

“…These genes are close to the red-eyed dilution (Brown et al, 1996; Prieur and Meyers, 1984). In contrast to dysfunctional 5-HT release from platelets, FH rats express increased levels of 5-HT and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA), in the brain and have altered responses to serotoninergic agents, indicating that FH rats have an altered serotoninergic system in the central nervous system (Gudelsky et al, 1985; Joseph, 1978). Therefore, FH rats are used as animal models for depression, but contrasting results have been reported regarding whether this strain can, in fact, model depression.…”

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“…After 1 or 2 h the rats were decapitated and blood and brains collected. Plasma tryptophan, brain tryptophan, 5-HT & 5-HIAA were determined fluorimetrically as previously described (Joseph, 1978) as was corticosterone (Mattingly, 1962). The experiments showed that the rise in brain tryptophan induced by restraint stress in rats (60.2% at 1 h and 39.7% at 2 h P < 0.001) was prevented by administration of valine 200 mg/kg i.p.…”